Effects of aging and the body mass index on male sex hormones: a cross-sectional study in 701 Brazilian men / Efeitos do envelhecimento e do índice de massa corporal sobre os hormônios sexuais masculinos: um estudo transversal em 701 homens brasileiros

Background: Some studies indicated that body mass index (BMI) is inversely proportional to serum testosterone concentrations in men. Purposes: This study aimed to analyze the effects of aging and obesity on total testosterone (TT), free testosterone (FT), bioavailable testosterone (BT), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels. Methods: A cross-sectional study was performed to assess the clinical and laboratory profiles of 701 patients treated at a private urology clinic in Ponta Grossa, Brazil, from January 2016 to December 2018. Results: Patients' age ranged from 16 to 88 years (mean, 56.9 ± 13.62 years). Age did not significantly influence serum TT concentrations, except compared to patients aged >70 years. However, changes were observed in FT and BT (p < 0.05). The mean SHBG increased with age (p < 0.05). A tendency toward LH elevation was observed in older patients, but it was not statistically significant. An inverse proportional relationship between TT, FT, and BT and the testosterone deficiency rate (TT < 300 ng/dL) was observed within BMI groups (p < 0.05). The testosterone deficiency rate was 21.5% in individuals with normal BMI, 29% in overweight individuals, and 37% in obese individuals. Conclusions: Aging affected the testosterone concentrations in men and became increasingly evident using FT and BT instead of TT. SHBG increased with age. Obesity was associated with a decrease in TT, FT, and BT but also increased the rate of hypogonadism. (AU)

Fundamentos: Alguns estudos indicam que o índice de massa corporal (IMC) é inversamente proporcional à con-centração de testosterona sérica em homens. Objetivos: O objetivo deste estudo é analisar o efeito do envelhe-cimento e da obesidade na testosterona biodisponível total e livre, bem como nos níveis de hormônio luteinizante e globulina ligadora de hormônio sexual. Métodos: Foi realizado um estudo transversal abordando o perfil clínico e laboratorial de 701 pacientes atendidos em uma clínica privada de urologia em Ponta Grossa, Brasil, de janei-ro de 2016 a dezembro de 2018. Resultados: A idade dos pacientes variou de 16 a 88 anos (média de 56,9 ± 13,62 anos). A idade não influenciou significativamente as concentrações séricas de testosterona total, exceto quando comparada a pacientes com mais de 70 anos. No entanto, foi observada diferença na testosterona livre e biodisponível (p <0,05). A média de globulina de ligação aos hormônios sexuais aumentou com a idade (p <0,05). Embora uma tendência à elevação da luteinização tenha sido observada em pacientes mais idosos, ela não foi significativa. Relação inversa entre testosterona total, livre e biodisponível e taxa de deficiência de testosterona (testosterona total <300 ng / dL) foi observada dentro dos grupos de índice de massa corporal (p <0,05). A taxa de deficiência de testosterona em indivíduos com índice de massa corporal normal foi de 21,5%, indivíduos com sobre-peso foi de 29% e em indivíduos com obesidade foi de 37%. Conclusões: O envelhecimento afetou a concentração de testosterona em homens, mais evidente ao avaliar testosterona livre e biodisponível em vez de testosterona total. A globulina de ligação aos hormônios sexuais aumentou com a idade. A obesidade foi associada à redução da testosterona total, livre e biodisponível e ao aumento da taxa de hipogonadismo. (AU)

Sex hormone binding globulin during an annual reproductive cycle in the hepatopancreas and ovary of pejerrey (Odontesthes bonariensis).

In the present study, we determined the hepatopancratic shbg transcript abundance and ovarian immunoreactive Shbg (ir-Shbg) localization in pejerrey females at different gonadal stages during an annual ovarian cycle. In the hepatopancreas, shbg expression remains was constant in pre-vitellogenic stages, decreased at final vitellogenesis to increase again in final maturation and atretic stages to previous levels at post-vitellogenic stages. Related to this, also we found a negative significant relation between sex steroid and shbg expression. On the other hand, in the ovary we found ir-Shbg inside of cortical alveoli, from previtellogenic stages to final maturation. This localization of Shbg in a teleost fish ovary suggests a new role for Shbg in oocytes, that may also extend the oocyte fertilization/development process.

Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

ABSTRACT Introduction and aim. Endogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD. Material and methods. A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (Cl) comparing between subjects with and without NAFLD by using random-effects model. Results. Sixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD. Conclusion. Our meta-analysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.

Sex hormone binding globulin: Expression throughout early development and adult pejerrey fish, Odontesthes bonariensis.

Sex hormone binding globulin (Shbg) is a plasma glycoprotein that binds and transports steroids in the blood of all vertebrate classes apart from birds. In the present study we characterized shbg from pejerrey, a fish species with a well characterized temperature-dependent sex determination. The pejerrey shbg mRNA comprises 1185bp encoding for a 395 amino acid Shbg precursor protein that includes a leader sequence for secretion. Relative quantification of shbg transcript abundance revealed expression early in development coinciding with the sex-determining period and probably in association with temperature leading to male determination. The hepatopancreas was the main site of shbg expression, which varied according to the sex cycle in females. It was also expressed in gills, gonads, gut and taste buds during both larval stages and in adult fish. The presence of Shbg in organs in close contact with the environment such as gills, pseudobranchs, gut and taste buds suggests that these are potential sources of uptake or release of steroids/xenosteroids to and from the aquatic environment.

[Female hyperandrogenemia and normal serum levels of testosterone and sex hormone binding globulin]. / Hiperandrogenemia femenina y niveles séricos normales de testosterona y globulina ligadora de esteroides sexuales.

It is well known that the reference values usually employed for endocrine biochemical measurements are those suggested by the suppliers of commercial kits despite their advice that each laboratory should set its own reference values. Our objectives were to (i) determine reference ranges for serum testosterone (T) and sex hormone binding globulin (SHBG) appropriate to our laboratory and population, and (ii) to analyze their influence on evaluating hyperandrogenemia. SHBG and T were measured, and free and bioavailable testosterone calculated, in (a) 30 selected non-hyperandrogenic women, (b) 87 non-selected healthy female blood donors, (c) 53 women with hyperandrogenism, and (d) 38 women with hyperandrogenic disorders but without biochemical hyperandrogenemia according to normal ranges suggested by the kit manufacturer. Mean serum SHBG concentrations were significantly different among all four groups. SHBG levels were significantly higher in selected normal women (group a). Using our results for this selected control group as new reference values, 12 out of 38 (31.6%) women with hyperandrogenic disorders without apparent hyperandrogenemia (group d) were recategorized as hyperandrogenemic. Similarly, 4 out of 63 (6.4%) non-selected, normal weight, women (group b), were recategorized as hyperandrogenic. Therefore, the diagnosis of hyperandrogenemia would improve accuracy by using customized reference SHBG values instead of those suggested by the suppliers.

Female hyperandrogenemia and normal serum levels of testosterone and sex hormone binding globulin

It is well known that the reference values usually employed for endocrine biochemical measurements are those suggested by the suppliers of commercial kits despite their advice that each laboratory should set its own reference values. Our objectives were to (i) determine reference ranges for serum testosterone (T) and sex hormone binding globulin (SHBG) appropriate to our laboratory and population, and (ii) to analyze their influence on evaluating hyperandrogenemia. SHBG and T were measured, and free and bioavailable testosterone calculated, in (a) 30 selected non-hyperandrogenic women, (b) 87 non-selected healthy female blood donors, (c) 53 women with hyperandrogenism, and (d) 38 women with hyperandrogenic disorders but without biochemical hyperandrogenemia according to normal ranges suggested by the kit manufacturer. Mean serum SHBG concentrations were significantly different among all four groups. SHBG levels were significantly higher in selected normal women (group a). Using our results for this selected control group as new reference values, 12 out of 38 (31.6%) women with hyperandrogenic disorders without apparent hyperandrogenemia (group d) were recategorized as hyperandrogenemic. Similarly, 4 out of 63 (6.4%) non-selected, normal weight, women (group b), were recategorized as hyperandrogenic. Therefore, the diagnosis of hyperandrogenemia would improve accuracy by using customized reference SHBG values instead of those suggested by the suppliers.

Con frecuencia los valores de referencia utilizados para las evaluaciones bioquímicas endocrinológicas son los sugeridos por los kits utilizados, a pesar de las recomendaciones de que cada laboratorio debiera obtener sus propios valores de normalidad. Nuestros objetivos fueron (i) analizar los rangos de referencia para testosterona (T) y globulina ligadora de esteroides sexuales (SHBG) apropiados para nuestro laboratorio y población, y (ii) analizar su influencia en la evaluación de la hiperandrogenemia. Se midió T y SHBG y se calculó testosterona libre y biodisponible en un grupo (a) control de 30 mujeres no hiperandrogénicas, (b) 87 mujeres no seleccionadas donantes de sangre, (c) 53 mujeres con hiperandrogenismo, y (d) 38 mujeres con desórdenes hiperandrogénicos pero sin hiperandrogenemia de acuerdo a los rangos de normalidad sugeridos por el kit. La concentración media de SHBG fue significativamente diferente entre los cuatro grupos. Los niveles de SHBG fueron significativamente más altos en las mujeres controles seleccionadas (grupo a). Tomando en consideración los resultados obtenidos en este grupo y estableciendo los rangos de referencia adecuados, 12 de 38 mujeres (31.6%) hiperandrogénicas sin hiperandrogenemia (grupo d) fueron recategorizadas como con exceso androgénico bioquímico. De igual manera, al analizar mujeres normopesas no seleccionadas, en edad reproductiva (grupo b), 4 de 63 (6.4%) pudieron ser definidas como hiperandrogénicas. Utilizando valores adecuados de referencia para SHBG, se mejora la precisión del diagnóstico de exceso androgénico.

Female hyperandrogenemia and normal serum levels of testosterone and sex hormone binding globulin

It is well known that the reference values usually employed for endocrine biochemical measurements are those suggested by the suppliers of commercial kits despite their advice that each laboratory should set its own reference values. Our objectives were to (i) determine reference ranges for serum testosterone (T) and sex hormone binding globulin (SHBG) appropriate to our laboratory and population, and (ii) to analyze their influence on evaluating hyperandrogenemia. SHBG and T were measured, and free and bioavailable testosterone calculated, in (a) 30 selected non-hyperandrogenic women, (b) 87 non-selected healthy female blood donors, (c) 53 women with hyperandrogenism, and (d) 38 women with hyperandrogenic disorders but without biochemical hyperandrogenemia according to normal ranges suggested by the kit manufacturer. Mean serum SHBG concentrations were significantly different among all four groups. SHBG levels were significantly higher in selected normal women (group a). Using our results for this selected control group as new reference values, 12 out of 38 (31.6%) women with hyperandrogenic disorders without apparent hyperandrogenemia (group d) were recategorized as hyperandrogenemic. Similarly, 4 out of 63 (6.4%) non-selected, normal weight, women (group b), were recategorized as hyperandrogenic. Therefore, the diagnosis of hyperandrogenemia would improve accuracy by using customized reference SHBG values instead of those suggested by the suppliers.(AU)

Con frecuencia los valores de referencia utilizados para las evaluaciones bioquímicas endocrinológicas son los sugeridos por los kits utilizados, a pesar de las recomendaciones de que cada laboratorio debiera obtener sus propios valores de normalidad. Nuestros objetivos fueron (i) analizar los rangos de referencia para testosterona (T) y globulina ligadora de esteroides sexuales (SHBG) apropiados para nuestro laboratorio y población, y (ii) analizar su influencia en la evaluación de la hiperandrogenemia. Se midió T y SHBG y se calculó testosterona libre y biodisponible en un grupo (a) control de 30 mujeres no hiperandrogénicas, (b) 87 mujeres no seleccionadas donantes de sangre, (c) 53 mujeres con hiperandrogenismo, y (d) 38 mujeres con desórdenes hiperandrogénicos pero sin hiperandrogenemia de acuerdo a los rangos de normalidad sugeridos por el kit. La concentración media de SHBG fue significativamente diferente entre los cuatro grupos. Los niveles de SHBG fueron significativamente más altos en las mujeres controles seleccionadas (grupo a). Tomando en consideración los resultados obtenidos en este grupo y estableciendo los rangos de referencia adecuados, 12 de 38 mujeres (31.6%) hiperandrogénicas sin hiperandrogenemia (grupo d) fueron recategorizadas como con exceso androgénico bioquímico. De igual manera, al analizar mujeres normopesas no seleccionadas, en edad reproductiva (grupo b), 4 de 63 (6.4%) pudieron ser definidas como hiperandrogénicas. Utilizando valores adecuados de referencia para SHBG, se mejora la precisión del diagnóstico de exceso androgénico.(AU)

Lipoprotein subclasses and endogenous sex hormones in women at midlife.

The objective of this work was to evaluate the associations between levels of endogenous sex hormones in women at midlife and lipoprotein subclasses. One hundred and twenty women (68 late peri-/postmenopausal and 52 pre-/early perimenopausal) from the Study of Women's Health Across the Nation (Pittsburgh site) were included. Lipoprotein subclasses were quantified using NMR spectroscopy. Participants (57.5% White and 42.5% Black) were 50.4 ± 1.9 years old. Adjusting for age, race, cycle day of blood draw, BMI, physical activity, and alcohol consumption, a negative correlation was found between estradiol (E2) and medium-small LDL particle (LDL-P) concentration (ρ = -0.19, P = 0.04). Further, E2 was positively correlated with HDL particle (HDL-P) size (ρ = 0.22, P = 0.02). For sex hormone binding globulin (SHBG), independent negative correlation was found with total small LDL-P concentration. SHBG was also positively correlated with LDL-P and HDL-P sizes (P < 0.05 for all). For free androgen index (FAI), positive correlations were found with concentrations of total VLDL particles, total LDL-Ps, and total small LDL-Ps. Additionally, FAI was negatively correlated with large HDL-P concentration, and HDL-P and LDL-P sizes (P < 0.05 for all). Lower levels of E2 and SHBG, and higher levels of FAI were associated with a more atherogenic profile of lipoprotein subclasses. Sex hormone levels at midlife may increase women's risk of coronary heart disease.

Association between sex hormone-binding globulin (SHBG) and metabolic syndrome among men / Associação entre globulina de ligação a hormônio sexual (SHBG) e síndrome metabólica em homens

CONTEXT AND OBJECTIVE: Metabolic syndrome consists of a set of factors that imply increased risk of cardiovascular diseases. The objective here was to evaluate the association between sex hormone-binding globulin (SHBG), sex hormones and metabolic syndrome among men. DESIGN AND SETTING: Retrospective analysis on data from the study "Endogenous oestradiol but not testosterone is related to coronary artery disease in men", conducted in a hospital in São Paulo. METHODS: Men (aged 40-70) who underwent coronary angiography were selected. The age, weight, height, waist circumference, body mass index and prevalence of dyslipidemia, hypertension and diabetes of each patient were registered. Metabolic syndrome was defined in accordance with the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII). Serum samples were collected to assess the levels of glucose, total cholesterol, HDL-cholesterol (high density lipoprotein), triglycerides, albumin, SHBG, estradiol and total testosterone (TT). The levels of LDL-cholesterol (low density lipoprotein) were calculated using Friedewald's formula and free testosterone (FT) and bioavailable testosterone (BT) using Vermeulen's formula. RESULTS: 141 patients were enrolled in the study. The prevalence of metabolic syndrome was significantly higher in the first SHBG tercile than in the second and third terciles. A statistically significant positive association between the SHBG and TT values was observed, but no such association was seen between SHBG, BT and FT. CONCLUSION: Low serum levels of SHBG are associated with higher prevalence of metabolic syndrome among male patients, but further studies are required to confirm this association. .

CONTEXTO E OBJETIVO: A síndrome metabólica (SM) consiste em um conjunto de fatores que implicam risco elevado para doenças cardiovasculares. O objetivo foi avaliar a associação entre a globulina ligadora de esteroides sexuais (SHBG), hormônios sexuais e a SM em homens. TIPO DE ESTUDO E LOCAL: Análise retrospectiva de dados do estudo "Estradiol mas não testosterona se correlaciona com doença arterial coronariana em homens", conduzido em um hospital em São Paulo. MÉTODOS: Foram selecionados pacientes do sexo masculino com idade entre 40 e 70 anos, submetidos a angiografia coronária. A idade, a prevalência de dislipidemia, hipertensão e diabetes, o peso, a altura, cintura e o índice de massa corpórea de cada paciente foram coletados. A definição de SM seguiu os critérios do NCEP-ATPIII. Amostras séricas foram coletadas para análises da glicose, colesterol total, colesterol-HDL (high density lipoprotein), triglicerídeos, albumina, SHBG, estradiol e testosterona total (TT). O colesterol-LDL (low density lipoprotein) foi calculado pela fórmula de Friedewald e as testosteronas livre (TL) e biodisponível (TB) pela fórmula de Vermeulen. RESULTADOS: Entraram no estudo 141 pacientes. A prevalência de SM foi significativamente maior no primeiro tercil de SHBG em comparação ao segundo e terceiro tercis. Foi verificada uma associação positiva e significativa ente os valores de SHBG e TT, porém essa associação não foi verificada entre SHBG e TB e TL. CONCLUSÃO: Baixos níveis séricos de SHBG estiveram associados com alta prevalência da SM em pacientes do sexo masculino. Faz-se necessário que estudos avaliem essa associação. .

Deficiencia de andrógenos y enfermedad cardiovascular en el hombre / Androgens deficiency and cardiovascular disease in the man

El hipogonadismo masculino, manifestado por la disminución de los niveles séricos de testosterona,representa una causa importante de morbimortalidad en pacientes mayores de 40 años. Su prevalencia es proporcional a la edad, y las diversas manifestaciones clínicas, de índole física, sicológica y sexual, conllevan a un marcado deterioro clínico del paciente. El impacto de la deficiencia de testosterona sobre el aparato cardiovascular acelera la progresión de la enfermedad coronaria, disminuye la sensibilidad a la insulina y aumenta la mortalidad global. Según la Sociedad Americana de Endocrinología,el diagnóstico bioquímico se realiza con valores de testosterona total <300 mg/dL. Definir el inicio de la terapia de reemplazo con testosterona siempre deberá incluir la clínica y las mediciones de laboratorio. El efecto sistémico de la terapia se verá reflejado en la mejoría de la fatiga, de la libido y del mejor control de los factores de riesgo cardiovascular, que incluye la disminución de la grasa visceral, mejoría de la sensibilidad a la insulina, del perfil lipídico, de las cifras de presión arterial y en algunos casos, disminución de la mortalidad.

Male hypogonadism, manifested by decreased serum testosterone levels, is an important cause of morbidity and mortality in patients older than 40 years. Its prevalence is proportional to age, and several clinical manifestations, as physical, psychological and sexual, lead to a marked clinical deterioration. The impact of testosterone deficiency on the cardiovascular system accelerates the progression of coronary artery disease, decreases insulin sensitivity and increases overall mortality. American Society for Endocrinology accepted serum values lower than 300 ng/dL as a diagnostic support. To define the start of testosterone replacement therapy should always include clinical and laboratory measurements. Systemic therapy effects will be reflected in the fatigue eradication, libido improvement, and better control of cardiovascular risk factors, including decreased abdominal fat, improved insulin sensitivity, lipid profile, arterial blood pressure, and in some cases, reduction of the mortality.

Serum levels of Sex Hormone Binding Globulin (SHBG) are not predictive of prostate cancer diagnosis and aggressiveness: results from an italian biopsy cohort

Purpose To explore the association between serum levels of Sex Hormone Binding Globulin (SHBG) and the risk of developing prostate cancer (PCa) as well as high grade disease in men undergoing prostate biopsy. Materials and Methods Between 2006 and 2012, we prospectively enrolled 740 patients with no history of PCa undergoing prostate biopsy. Before biopsy general data of the patient DRE, PSA and BMI were recorded. The risk of detecting cancer and high grade cancer was assessed as a function of SHBG using crude and adjusted logistic regressions. Results Serum levels of SHBG were not associated with an increased risk of PCa or high grade disease. Age (OR 1.027 95% CI 1.003-1.052 p = 0.027), DRE (OR 3.391 95% CI 2.258-5.092 p = 0.000) and PSA (OR 1.078 95% CI 1.037-1.120 p = 0.000) were found to be independent predictors of prostate cancer risk. Age (OR 1.051 95% CI 1.009-1.095 p = 0.016), DRE (OR 2.519 95% CI 1.384-4.584 p = 0.000), BMI (OR 1.098 95% CI 1.011-1.193 p = 0.027) and PSA (OR 1.074 95% CI 1.014-1.137 p = 0.015) were found to be independent predictors of high grade disease. Conclusions In our cohort of patients, serum levels of SHBG are not predictive of PCa or high grade disease. According to our experience SHBG should not be considered a biomarker in PCa diagnosis neither a marker for high grade disease. .

Evaluación de la globulina transportadora de hormonas esteroidales (SHBG) durante el embarazo como factor predictor de pre-eclampsia y restricción del crecimiento intrauterino / Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction

Background: Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). Aim: To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Patients and Methods: Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselectedpregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Results: Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Conclusions: Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.